Sphingosine 1-phosphate stimulates rho-mediated tyrosine phosphorylation of focal adhesion kinase and paxillin in Swiss 3T3 fibroblasts.
Sphingosine 1-phosphate stimulates rho-mediated tyrosine phosphorylation of focal adhesion kinase and paxillin in Swiss 3T3 fibroblasts.
复制标题
1-磷酸鞘氨醇刺激瑞士 3T3 成纤维细胞中粘着斑激酶和桩蛋白的 rho 介导的酪氨酸磷酸化。
DOI：
10.1042/bj3240481
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Spiegel,S
中科院分区：
文献类型：
--
作者：
Wang,F;Nobes,CD;Hall,A;Spiegel,S
鞘氨醇1-磷酸（SPP），一种涉及血小板衍生生长因子的促有丝分裂作用的鞘脂第二信使[Olivera，A.和Spiegel，S.（1993）Nature（伦敦）365，557-560]诱导肌动蛋白细胞骨架的快速重组，导致应力纤维形成。SPP还诱导黏着斑激酶（p125 FAK）和细胞粘附素相关蛋白桩蛋白的瞬时酪氨酸磷酸化，黏着斑激酶是一种定位于黏着斑的胞质酪氨酸激酶。外切酶C3转移酶，ADP-核糖基化Rho（Ras相关的小GTP结合蛋白）天冬酰胺-41，使其生物活性，抑制应激纤维的形成和蛋白酪氨酸磷酸化诱导的SPP。因此，Rho可能是应激纤维形成和p125 FAK和桩蛋白酪氨酸磷酸化的上游调节因子。蛋白激酶C（PKC）激活剂PMA预处理可抑制1-油酰溶血磷脂酸（LPA）诱导的应激纤维形成，但对SPP无抑制作用。同样地，PMA也降低了LPA诱导的p125 FAK和桩蛋白的酪氨酸磷酸化，而没有消除对SPP的反应。因此，PKC参与LPA依赖性信号传导，而不是SPP依赖性信号传导。聚阴离子药物苏拉明是一种广泛特异性的配体-受体相互作用抑制剂，它既不抑制SPP的促有丝分裂作用，也不抑制其对p125 FAK酪氨酸磷酸化的刺激。而苏拉明可明显抑制LPA诱导的上述反应。这些结果表明，与LPA相反，SPP可能在Swiss 3 T3成纤维细胞中作用于细胞内，刺激p125 FAK和桩蛋白的酪氨酸磷酸化和细胞生长。
Sphingosine 1-phosphate (SPP), a sphingolipid second messenger implicated in the mitogenic action of platelet-derived growth factor [Olivera, A. and Spiegel, S. (1993) Nature (London)365, 557–560], induced rapid reorganization of the actin cytoskeleton resulting in stress-fibre formation. SPP also induced transient tyrosine phosphorylation of focal adhesion kinase (p125FAK), a cytosolic tyrosine kinase that localizes in focal adhesions, and of the cytoskeleton-associated protein paxillin. Exoenzyme C3 transferase, which ADP-ribosylates Rho (a Ras-related small GTP binding protein) on asparagine-41 and renders it biologically inactive, inhibited both stress-fibre formation and protein tyrosine phosphorylation induced by SPP. Thus Rho may be an upstream regulator of both stress-fibre formation and tyrosine phosphorylation of p125FAKand paxillin. Pretreatment with PMA, an activator of protein kinase C (PKC), inhibited the stimulation of stress-fibre formation induced by 1-oleoyl-lysophosphatidic acid (LPA) but not that by SPP. Similarly, PMA also decreased LPA-induced tyrosine phosphorylation of p125FAKand paxillin without abrogating the response to SPP. Thus PKC is involved in LPA- but not SPP-dependent signalling. The polyanionic drug suramin, a broad-specificity inhibitor of ligand–receptor interactions, did not inhibit either the mitogenic effect of SPP or its stimulation of tyrosine phosphorylation of p125FAK. However, suramin markedly inhibited these responses induced by LPA. These results suggest that in contrast with LPA, SPP may be acting intracellularly in Swiss 3T3 fibroblasts to stimulate tyrosine phosphorylation of p125FAKand paxillin and cell growth.